D-GL (D-glutamic acid:D-lysine copolymer) conjugates have been described at considerable length and various applications of D-GL conjugates of various immunologically reactive species have been reported. The following U.S. Pat. Nos. describe in considerable detail the chemistry of D-GL and method of forming conjugates thereof: 4,191,668; 4,220,565; 4,222,907; 4,253,995; 4,253,995; 4,276,206; and 4,388,441. The technology underlying the invention is found in any of several treatises and reports of current advances, including, for example: METHODS IN ENZYMOLOGY, Academic Press, New York, e.g. in Volume 58, Cell Culture and Volume 68, Recombinant DNA; CELL BIOLOGY, Academic Press, New York (3 volumes); METHODS IN MOLECULAR BIOLOGY, Humana Press, Clifton, New Jersey; ADVANCES IN IMMUNOPHARMACOLOGY, Pergamon Press, New York; ADVANCES IN ALLERGOLOGY AND IMMUNOLOGY, Pergamon Press, New York, and in the current technical and patent literature.
The immunochemistry of D-GL conjugates is discussed and specific examples of immunochemical reaction, conjugation, and applications in diagnosis and treatment are discussed in the literature. See, for example, the above listed U.S. Pat. Nos. and the following publications. Katz, David H.; Davie, J. M.; Paul, W. E.; Benacerraf, Baruj J. Exp. Mid. 1971 134(1) :201-223; Nossal, J. V.; Davie, J. M.; Paul, W. E.; Katz, David H.; Benacerraf, Baruj J. Exp. Med. 1972 136(3) :426-438; Katz, David H.; Toshiyuki, H.; Benacerraf, Baruj J. Exp. Med. 1972 136(6) :1404-1429; Nossal, J. V.; Pike, B. L.; Katz, David. H. J. Exp. Med. 1973 138(1) :312-317; Osborne, D. P.; Katz, David. H. J. Exp. Med. 1973 137(4) :991-1007; Katz, David H.; Toshiyuki, H.; Benacerraf, Baruj Proc. Nat. Acad. Sci. USA 1973 70(10) :2776-2780; Toshiyuki, H.; Katz, David H. J. Exp. Med. 1974 139:1446-1463; Katz, David H.; Toshiyuki, H.; Benacerraf, Baruj J. Exp. Med. 1974 139:1464-1471; Katz, David H.; Benacerraf, Baruj Immunol. Tol. 1974, 189-201 and 249-281; J. Immunol. 1974, 112(3) :1158-1163; Ault, K. A.; Unanue, E. R.; Katz, David H. Proc. Natl. Acad. Sci. U.S.A. 1974, 71(8) :3111-3114; Eshhar, z.; Benacerraf, B; Katz, David H. J. Immunol. 1975, 114(2) :872-876; Katz, David H.; Stechsulte, D. J.; Benacerraf, Baruj J. Allerg. Clin. Immunol. 1975 55(6) :403-410; Bullock, W. W., Katz, David H., Benacerraf, Baruj J. Immunol. 1975 115 (1) :272-277;Mosier, D. E. Nature (London 1975:257:141-3; Bitter-Suermann, D.; Hadding, U.; Schorlemmer, H. U.; Limbert, M.; Dierich, M.; Dukor, P.J. Immunol. 1975 115(2) :425-30; Chiorazzi, N; Eshhar, Z; Katz, David H. Proc. Natl. Acad. Sci. U.S.A. 1976 73(6) :2091-5; Katz, David H.; Borel, Y. J. Immunol. 1978 120(6) :1824-1827; Liu, Fu-Tong; Katz, David H. Proc. Natl. Acad. Sci. USA 1979 76(3) :1430-1434; Liu, Fu-Tong; Bogowitz, C. A.; Bargatze, M. Z; Katz, Lee R.; Katz, David H. J. Immunol. 1979 123(6) :2456-2465; Katz, David H. and Liu, Fu-Tong, ADVANCES IN ALLERGOLOGY AND IMMUNOLOGY, Ed. Oehling, A., Pergamon Press, New York (1980) pp. 51-59; Liu, Fu-Tong; Bargatze, R. F.; Katz, David H. J. Allerg. Clin. Immunol. 1980 66(4) :322-326; Katz, David H. and Liu, Fu-Tong, ADVANCES IN IMMUNOPHARMACOLOGY, Ed. Hadden, J., Pergamon Press, New York (1980) pp. 277-284; Klinman, N. R.; Schrater, A. F.; Katz, David H.J. Immunol. 1981 126(5) :1970-1973.
The published literature describes research into various immunochemical phenomena in an effort to understand the chain of immunological events and diagnostic methods and processes for detecting immunological species, e.g. antigens, haptens or antibodies to antigens or haptens.
The ability of D-GL conjugates to induce tolerance to a variety of antigens, haptens, nucleotides, nucleosides, etc. is described and the ability of such conjugates to suppress antibody responses is mentioned, see, e.g., U.S. Pat. No. 4,191,668, David H. Katz, Mar. 4, 1980.
The underlying premise in prior art methods and approaches is ability of selected D-GL-antigen conjugates to interfere with the induction of antibody responses and thereby modify, reduce or prevent the production of antibodies. In the process of studying antibody tolerance, it has been discovered that D-GL conjugates of cell surface receptor binding molecules which bind by specific receptors on the surface of cells and membranes stabilize such cell surface receptor binding molecules at the specific site and modifies, slows or prevents ingestion and/or migration of the receptor. This discovery has both therapeutic and diagnostic implications. For example, it is a feature of this invention to use cell surface bonding molecule-D-GL conjugates to permit imaging of membranes, tumors, organs, etc. and to treat the surfaces of cells, membranes, tumors and organs by stabilizing cell surface receptor binding molecules which bind to receptor sites thereon. It is also a feature of this invention to treat membranes, tumors and the like by applying to the surface thereof cell surface binding molecule--D-GL conjugates to modify, slow or prevent the normal response of the cell surface receptor when coupled with a normal cell surface binding molecule.